Study of the response of PCOS patients to clomiphene citrate based on hormonal Parameters and body mass index

Background: Our study aimed to evaluate the response of polycystic ovarian syndrome patients to clomiphene citrate based on hormonal parameters and body mass index.Methods: It is a prospective observational study that was carried out on 48 women with PCOS-related infertility. They were treated with an incremental dose of clomiphene citrate starting with 50 mg/day to a maximum of 100 mg. The response was recorded as either the presence or absence of ovulation. Hormonal parameters such as serum FSH, LH, testosterone, fasting insulin, DHEA, prolactin, and body mass index (BMI) were evaluated. The correlation of each of these parameters in predicting non-responsiveness (failure to ovulate with 100 mg clomiphene) was calculated.Results: Among 48 PCOS patients who were enrolled in the study, 14 patients responded to CC 50 mg, 26 patients responded to CC 100 mg and 8 patients were CC non-responders. We concluded that serum LH, fasting insulin, and BMI were significant predictors of response to ovulation with CC in PCOS patients.Conclusions: In our study, we concluded that among the hormonal and biochemical parameters we studied serum LH, fasting insulin, and BMI are significant predictors of response of ovulation with CC in women with PCOS-related infertility. This may help physicians to counsel and select the proper infertility treatment for women with PCOS experiencing infertility so that it should be less time-consuming and cost-effective.

The quest for better outcomes: a randomized controlled trial comparing letrozole versus clomiphene citrate in polycystic ovarian syndrome related infertility

Background: Infertility is a widespread concern, particularly among individuals with polycystic ovarian syndrome (PCOS). Clomiphene citrate (CC) has been a primary treatment for PCOS-related infertility, despite suboptimal pregnancy rates. Letrozole, an aromatase inhibitor, presents an alternative with potential advantages for improving pregnancy outcomes. This study aimed to rigorously compare letrozole and CC in the context of PCOS-related infertility, focusing on Bangladeshi women, adopting incremental dosing protocols, and examining endpoints to contribute valuable insights.Methods: A randomized controlled trial was conducted at a tertiary care center in Bangladesh from July 2021 to June 2023. Participants included women aged 18-35 with anovulatory infertility due to PCOS. They were randomized into two groups: letrozole and CC. Treatments were administered following incremental dosing protocols, and outcomes included endometrial thickness, ovulation rate, mono-follicular development, pregnancy rate, and time to pregnancy.Results: Out of 187 patients assessed for eligibility, 102 were enrolled, with 51 in each group. Demographics were comparable between groups. While endometrial thickness did not significantly differ between the groups, letrozole demonstrated a higher rate of mono-follicular development (72.55% versus 50.98%), a significantly higher pregnancy rate (47.06% versus 23.53%), and a shorter time to pregnancy (9.23 weeks versus 11.7 weeks) compared to CC.Conclusions: This study suggests that letrozole may be a preferred option for ovulation induction in PCOS patients due to its superior pregnancy rates and shorter time to pregnancy compared to CC. However, limitations such as a relatively small sample size and variations in dosages should be considered. Further research is needed to validate these findings and address the evolving needs of patients with PCOS-related infertility.

The effect of letrozole vs clomiphene citrate for ovulation induction in patients of infertility with polycystic ovarian syndrome

Background: The overall prevalence of primary infertility in India is 3.9% to 16.8%. PCOS being a recognized cause of infertility, affects 8 to 13% of all reproductive-age women. Clomiphene citrate (CC) is most commonly used as first line drug for ovulation induction. CC is selective estrogen receptor modulator (SERM) and has adverse effect on cervical mucus and endometrial receptivity resulting in low pregnancy rates. Letrozole an aromatase inhibitor is considered as better alternative drug due to its benefits over CC. Thus, the aim of the present study is to assess the effect of letrozole and clomiphene citrate for ovulation induction in women with PCOS and compare the pregnancy rates.Methods: This is a hospital based randomized controlled study conducted on 89 patients at Armed forces medical college in western Maharashtra from June 2019 to May 22. Women with infertility due to PCOS attending OPD/IPD who fulfilled the inclusion criteria were included in the study. The subjects were divided into two groups through computer generated randomization and Group A of 45 subjects received letrozole for ovulation induction while Group B with 44 subjects received clomiphene citrate (CC). Data was analyzed and comparison among the study groups was done with the help of unpaired t test or Mann-Whitney test.Results: The number of mature follicles after treatment was significantly greater in clomiphene citrate group (1.59 � 1.04) as compared to letrozole (1.02 � 0.76). However, there was statistically significant greater mono ovulation with letrozole (55.2% vs 40.3%, p=0.03). After ovulation induction, the mean endometrial thickness was significantly greater in letrozole group as compared to CC (9.85�32 mm vs. 8.45�53 mm; p<0.05). Ovulation rate with letrozole was 42.5% vs 32.5% and pregnancy rate was letrozole 20% vs CC 7.5% which was statistically significant (p<0.05).Conclusions: Letrozole is a better drug for ovulation induction in women with PCOS with an ovulatory cycles as pregnancy rates are higher and lesser chance of multiple pregnancy.

Effect of Clomiphene Citrate on the Ultrastructure of Testis in Albino Rats

SUMMARY: The aim of the present work was to study the closer effect of clomiphene citrate on the ultrastructure of the testis of adult albino rats to provide a basis for optimizing this drug in the treatment of male infertility. The testes were removed from both groups under anesthesia and then prepared for examination by light using hematoxylin and eosin stains and a transmission electron microscope. Semithin sections were cut into 1 µm thick sections, stained with toluidine blue, and examined by light microscopy for a survey. The desired areas were placed in the center, and other areas were trimmed. Primary spermatocytes showed marked nuclear changes (pyknosis), and their nuclear membranes were ill-defined and disrupted. The cytoplasm showed widespread degeneration of mitochondria and lysosomes and focal degeneration of the rough endoplasmic reticulum compared with the control group. The spermatids were pale, and the two phases of spermatogenesis were distinctly identifiable in the control group but were confused in the treated group. Some spermatids had interrupted nuclear membranes, also containing degenerated mitochondria, focal fragmentation of rough endoplasmic reticulum, and free ribosomes. Spermatozoa in the treated group appeared deformed compared to the control, where they had deformed head caps. Leydig cells of the treated group have an irregularly shaped nucleus, with focal chromatin aggregation and peripheral chromatin condensation on the inner surface of the nuclear membrane. The observations of the present work indicate a possible causal relationship between testicular affection and ingestion of clomiphene citrate, which can be avoided by close medical observations using ultrasonography, semen analysis, or testicular biopsy to detect early malignant changes. Furthermore, the drug should not be used for more than three to six cycles and should be stopped for at least three cycles before reuse. When clomiphene citrate is ineffective in the treatment of male infertility, human menopausal gonadotropin (hMG) administration is typically selected. However, high-dose hMG therapy is associated with a variety of adverse effects. In this work, we report the success of a modified clomiphene citrate regimen in increasing sperm count without any hazards to the testicular tissue.

El objetivo del trabajo fue estudiar el efecto del citrato de clomifeno sobre la estructura de los testículos de la rata albina adulta, con la finalidad de determinar la mejor manera de utilizar este fármaco en el tratamiento de la infertilidad masculina. Los testículos se extrajeron bajo anestesia y para su análisis a través de microscopio de luz se tiñeron con HE. Además, las muestras fueron preparadas para su examen con microscopía electrónica de transmisión. Por otra parte, se cortaron secciones semifinas de 1 µm de espesor, se tiñeron con azul de toluidina y se examinaron mediante microscopía óptica. Los espermatocitos primarios mostraron cambios nucleares marcados (picnosis) y sus membranas nucleares estaban mal definidas y alteradas. En el grupo experimental las células presentaban el citoplasma con degeneración generalizada de las mitocondrias y de los lisosomas y una degeneración focal del retículo endoplásmico rugoso en comparación con el grupo control. Las espermátidas estaban pálidas y las dos fases de la espermatogénesis eran claramente identificables en el grupo control, pero se confundían en el grupo tratado. Algunas espermátidas tenían membranas nucleares interrumpidas, y también contenían mitocondrias degeneradas, fragmentación focal del retículo endoplásmico rugoso y ribosomas libres. Los espermatozoides del grupo tratado se presentaban deformados en comparación con el control. Las células de Leydig del grupo tratado presentaban un núcleo de forma irregular, con agregación focal de cromatina y condensación de cromatina periférica en la superficie interna de la membrana nuclear. Las observaciones del presente trabajo indican una posible relación causal entre la afección testicular y la ingestión de citrato de clomifeno, que puede evitarse mediante observaciones médicas minuciosas a través de ecografía, análisis de semen o biopsia testicular para detectar cambios malignos tempranos. Además, el medicamento no debiera ser usado durante más de tres a seis ciclos y debe suspenderse durante al menos tres ciclos antes de volver a usarlo. Cuando el citrato de clomifeno es ineficaz en el tratamiento de la infertilidad masculina, normalmente se selecciona la administración de gonadotropina menopáusica humana (hMG). Sin embargo, la terapia con hMG en dosis altas se asocia con una variedad de efectos adversos. En este trabajo, informamos el éxito de un régimen modificado con citrato de clomifeno para aumentar el recuento de espermatozoides sin riesgo para el tejido testicular.

Protective Effect of Coscinium fenestratum Bark Extract on Letrozole Induced Polycystic Ovary Syndrome (PCOS) in Sprague Dawley Rats

Aim: Polycystic ovary syndrome (PCOS) is a common endocrine disorder. The aim of the present study is to evaluate the effects of the oral administration of Coscinium fenestratum bark extract in letrozole-induced PCOS in rats. Methods: Thirty female Sprague-Dawley (SD) rats were randomly divided into five groups of 6 animals each. Letrozole (1?mg/kg) was administered orally for a period of 21?days to induce PCOS. Control rats received 1?mL/day of distilled water, and the three groups of PCOS rats were given 1mg/kg of clomiphene citrate, 250 mg/kg of Coscinium fenestratum extract and 500 mg/kg of Coscinium fenestratum extract by oral gavage for 15 days. Blood samples were collected and the ovary of rats was removed, weighed, and fixed in 10% buffered formalin to determine the hormonal and antioxidant parameters. Results: In rats treated with BECF, significant increase in Catalase, Superoxide Dismutase and Lipid peroxidation level was decreased when compared with letrozole group. Histopathology showed that the BECF treated rats had normal ovarian structure, which was seen distorted due to the PCOS condition in letrozole treated rats. The results show significant decrease in total testosterone level and LH and significant increase in FSH. Therefore, the extract of BECF show significant effect on PCOS rats. The significance p value is >0.001. Conclusion: Based on these result, the BECF extract and traditional wisdom of this plant when used regularly can be a good treatment a suitable treatment option for PCOS which can be regularly used.

Treatment of Infertility in Women with Polycystic Ovary Syndrome in a Single Center Study

Background: Anovulatory infertility is caused by polycystic ovarian syndrome in 80 percent of patients. Preconception guidelines, such as lifestyle modification (weight loss) to avoid fetal neural tube abnormalities, and quitting smoking and drinking alcohol, are all part of the early treatment. A clomiphene citrate medication for timed intercourse is the first-line pharmacological treatment for producing ovulation. Exogenous gonadotropins or laparoscopic ovarian surgery are two options for second-line pharmaceutical treatment (ovarian drilling). Ovulation induction using clomiphene citrate or gonadotropins is effective, with a 70 % cumulative live birth rate. When laparoscopy is necessary, ovarian drilling should be done; this operation is usually successful in around half of the instances. Finally, when the previous interventions have failed, a high-complexity reproduction treatment (in vitro fertilization or intracytoplasmic sperm injection) is recommended. There is no evidence that metformin should be used routinely in the treatment of infertility in anovulatory women with polycystic ovary syndrome. Aromatase inhibitors show promise, but more research is needed to confirm their safety.Methods:This study was conducted in Department of gynecology and obstetrics, Dhaka Medical College Hospital, Dhaka, from January 2019 to December 2019. A total number of 100 patients with multiple myeloma were analyzed cytogenetically by interphase fluorescence in situ hybridization (iFISH). The collected data were analyzed by using the Statistical Package for Social Science (SPSS-24) for windows version 24.0.Conclusion:PCOS is a frequent syndrome and the most frequent cause of infertility. PCOS is defined as a syndrome with at least two of three of the Rotterdam criteria. A complete evaluation of the infertility is needed to exclude other causes of infertility..

Efeitos do citrato de clomifeno, letrozol e estradiol sobre apoptose em células do cumulus oophorus humano / Effects of clomiphene citrate, letrozole and estradiol on apoptosis in human cumulus oophorus cells

Citrato de clomifeno (CC) e letrozol (LE) são indutores de ovulação que, apesar das altas taxas de ovulação confirmada, atingem baixas taxas de gravidez. Este estudo teve como objetivo investigar os efeitos de CC e LE in vitro, isoladamente ou em combinação com estradiol (E), na apoptose de células do cumulus oophorus humano. Realizamos um estudo prospectivo controlado utilizando culturas primárias de células do cumulus de pacientes submetidas à fertilização in vitro (n=22). A coloração com Giemsa e a imunocitoquímica para alfa-inibina foram utilizadas para avaliar a pureza e a morfologia da cultura celular. A viabilidade celular foi avaliada pelo ensaio MTT, o ciclo celular por citometria de fluxo e a expressão gênica de Caspase-3, Bax e Superóxido dismutase 2 (SOD-2) e S26 por reação em cadeia de polimerase (PCR) em tempo real. As células foram tratadas por 24 horas em 5 grupos de tratamento: CC, CC + E, LE, LE + E e controle. Nenhum dos tratamentos afetou a viabilidade celular, mas o LE reduziu a porcentagem média de células na fase S em relação ao controle (24,79 versus 21,70, p=0,0014). O tratamento com CC aumentou a expressão gênica de Bax (4 vezes) e SOD-2 (2 vezes), que foi revertida quando adicionado E à cultura. A expressão de SOD-2 aumentou em células tratadas com LE quando comparado ao controle (4 vezes), que foi também revertida por adição de E. Estes achados sugerem que CC e LE não afetam significativamente a viabilidade das células do cumulus humana. Porém, houve modulação na expressão de genes envolvidos na apoptose por essas drogas isoladamente e em associação com E, sugerindo que CC e LE podem ter efeitos diretos nas células do cumulus além de seus mecanismos de ação conhecidos.

Clomiphene citrate (CC) and letrozole (LE) are ovulatory stimulants that, despite high ovulation rates, achieve low pregnancy rates. This study aimed to investigate the in vitro effects of CC and LE, alone or in combination with estradiol (E), on apoptosis in human cumulus cells. We performed a controlled prospective study using primary cumulus cell cultures from patients undergoing in vitro fertilization (n=22). Giemsa stain and alpha-inhibin immunocytochemistry was used to assess cell culture purity and morphology. Cell viability was evaluated by MTT assay, cell cycle status by flow cytometry, and Caspase-3, Bax and superoxide dismutase 2 (SOD-2), and S26 gene expression by real-time polymerase chain reaction (qPCR). Cells were treated for 24 hours in 5 conditioned media: CC, CC + E, LE, LE + E and control. None of the treatments affected cell viability, but LE reduced the mean percentage of cells in the S phase compared to control (24.79 versus 21.70, p=0.0014). CC treatment increased mRNA expression of Bax (4 fold) and SOD-2 (2 fold), which was reversed by co-treatment with E. SOD-2 expression increased in cells treated with LE compared to control (4 fold), which was also reversed by E. These findings suggest that CC and LE do not significantly affect the viability of human cumulus cells. Still, the expression of genes involved in apoptosis was modulated by these drugs alone and in association with E, suggesting that CC and LE may have direct effects on cumulus cells beyond their known mechanisms of action.

Atualizações na terapêutica farmacológica para infertilidade na mulher diagnosticada com síndrome de ovários policísticos: revisão de literatura / Updates on pharmacological treatments for infertility in women diagnosed with polycystic ovary syndrome: a literature review

Objetivo: Abordar atualizações referentes à terapia medicamentosa para indução da ovulação nas mulheres diagnosticadas com síndrome dos ovários policísticos (SOP). Métodos: Revisão de literatura por meio de levantamento bibliográfico do período de 1975 a 2021, nas bases eletrônicas PubMed, SciELO e MedLine, complementado pela Diretriz Internacional Baseada em Evidências para a Avaliação e Manejo da SOP de 2018 e pelo manual da Febrasgo para SOP. Sete descritores que atendessem à finalidade da pesquisa foram utilizados. Resultados: A literatura aponta atualmente algumas drogas como opção na terapêutica para a indução de ovulação, como metformina, letrozol e citrato de clomifeno, evidenciando que o uso de letrozol isolado e em associação com a metformina apresentaram melhores taxas de ovulação, 71,5% e 75,4%, respectivamente. Conclusão: O uso do letrozol isolado ou combinado com a metformina apresentou os melhores resultados nas taxas de gravidez e ovulação, todavia o tratamento para indução ovulatória deve ser individualizado.(AU)

Objective: To address updates of medicinal therapy for ovulation induction in women diagnosed with polycystic ovary syndrome (PCOS). Methods: Reviewing Literature through a bibliographic survey from 1975 to 2021, on the electronic databases PubMed, SciELO and MedLine, complemented by the International Evidence-Based Guideline for the Evaluation and Management of PCOS 2018 and the Febrasgo guide for PCOS. Seven descriptors that matched to the purpose of the research were applied. Results: Some drugs are currently indicated in the literature as an option for ovulation induction therapy, such as: metformin, letrozole and clomiphene citrate, showing that the use of letrozole alone and in association with metformin had better ovulation rates, 71.5% and 75.4%, respectively. Conclusion: The use of letrozole alone or combined with metformin showed the best results in pregnancy and ovulation rates, however, treatment for ovulatory induction must be individualized.(AU)

Clomiphene versus letrozole: a better agent for ovulation induction

Background: Anovulatory dysfunction is a commonly encountered problem which is responsible for about 40% of female infertility. One of the leading causes of female infertility is polycystic ovarian syndrome (PCOS). Clomiphene citrate has been the drug of choice in treating women with anovulatory infertility. However, in recent years, letrozole, an aromatase inhibitor, has emerged as alternative ovulation induction agent. Aim of this study was to compare efficacy of clomiphene citrate and letrozole as first line therapy for ovulation induction in polycystic ovarian syndrome.Methods: This study was a hospital based prospective comparative study done in MVJ MC and RH involving 100 females suffering from infertility due to anovulation. They were divided into 2 groups of 50 each. One group was given clomiphene citrate 50 mg while another group was given letrozole 2.5 mg from day 3 to day 7 of menstrual cycle. Ultrasonographic follicular monitoring was done and injection beta HCG 5000 IU was given once follicle reached optimum size (≥18 mm) and endometrial thickness was adequate (≥7 mm). Patients were advised for timed intercourse after 24-36 hours of HCG administration. Ovulation was detected by sonographic findings of follicular rupture done after 48 hours. Primary outcomes measured were number of growing follicles (≥18 mm), endometrial thickness, ovulation rate and pregnancy rate.Results: In our study there was significant difference in the outcomes of ovulation induction between letrozole group and clomiphene group.  Women who received letrozole showed improved endometrial growth (8.44 mm versus 7.86 mm), ovulation rate (72% versus 56%) and pregnancy rate (22.2% versus 14.3%) than those who received clomiphene. However, variation in follicular growth was negligible between the two groups (1.28 versus 1.36).Conclusions: Letrozole is a superior alternative to clomiphene citrate for ovulation induction in cases of PCOS with anovulatory menstrual cycle, and can be considered as first-line therapy for ovulation induction in such women.

Study of hundred cases of infertility in polycystic ovarian syndrome and its management outcome

Background: Polycystic ovarian syndrome (PCOS) is relatively common endocrine disorder in reproductive aged women, which leads to reproductive, metabolic and endocrine abnormality. About 70 to 80% patients with PCOS have complained of infertility due to anovulation. Due to advanced diagnostic facility by endoscopic evaluation in infertility, incidence of PCOS has increased now a days.Methods: This is study of 100 cases of infertility with polycystic ovarian syndrome and its pregnancy outcome. In this study, from May 2019 to April 2020, 100 cases of infertility with PCOS were studied at tertiary care hospital. Hormonal assay, ultrasound and laparoscopy were used as diagnostic technique. Clomiphene citrate, letrozole, metformin, and laparoscopic ovarian drilling were used as treatment modalities.Results: The maximum number of patients in the study group are seen in the age group of 21-25 years. Menstrual irregularities are the most common presenting symptom affecting 70% females. Primary infertility is most commonly associated with PCOS. In PCOS, there is increased LH:FSH ratio. On USG examination, there are enlarged ovaries in 82% cases.Conclusions: PCOS is an emerging disease of new generation with high prevalence in infertile women. After proper diagnosis, management with lifestyle modification, pharmacotherapy with clomiphene citrate, letrozole and metformin are used as per necessities. Operative laparoscopy with ovarian drilling is the main treatment which results in good conception rate.

Comparison of pregnancy outcome between clomiphene citrate and sequential clomiphene citrate+human menopausal gonadotropin in intrauterine insemination

Background: Intrauterine insemination (IUI) has been widely used as a common treatment for infertile couples. This study compares the sequential clomiphene citrate (CC) treatment with CC and human menopausal gonadotropin (hMG) treatment in women undergoing IUI. Therefore, this study was designed to determine the effects of addition of gonadotropin (CC+hMG) would improve the pregnancy rate in women undergoing IUI. And also compare the sequential CC+hMG treatment with CC treatment in women undergoing IUI. Methods: A cross-sectional study design was conducted at D. Y. Patil Fertility Centre, D.Y Patil Hospital, Navi Mumbai from September 2018 to August 2019. Source populations were all patients who live in Mumbai, Maharashtra, India. A total of 67 patients were enrolled in this study. (It consisted of 67 sub fertile couples undergoing ovarian stimulation for IUI cycles). Results: There was no significant difference between the two studied groups regarding endometrial thickness (8.3±2.1 versus 9.7±2.8, respectively), number of mature follicles on the day of hCG injection (3.3±1.2 versus 3.5±1.1, respectively) and, but there was significant difference between the CC+hMG group and CC group regarding the total dose of gonadotropins used in ovulation induction (305±23.8 versus 655±192; total IU, respectively) p<0.05. Conclusions: Women undergoing IUI, ovarian stimulation CC combined with hMG, significantly improved the pregnancy and live birth rates as compared to that of CC group. In women undergoing ovarian stimulation and IUI, there are no significant differences in pregnancy and live birth rates among the various stimulation protocols.

Lomiphene citrate versus letrozole as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome women: a prospective randomized controlled trial

Background: The present study was design to compare letrozole (5 mg) and clomiphene citrate (100 mg) as first line ovulation induction drug in infertile anovulatory polycystic ovarian syndrome (PCOS) women.Methods: This prospective randomized clinical trial included 60 cases of PCOS with anovulatory infertility. The first group comprised of 30 patients who received 5 mg letrozole daily and the second group received 100 mg clomiphene citrate daily for 5 days starting on day 2-5 of menses. Both the groups were followed by ultrasound for follicle monitoring, ovulation and endometrial thickness. When dominant follicle reaches a diameter of more than or equal to 18mm and endometrial thickness ≥7.5 mm, human chorionic gonadotrophin (hCG) 5,000 IU was given intramuscularly and timed intercourse was advised. Main outcome measures were occurrence of ovulation, endometrial thickness and pregnancy rates.Results: The mean age, body mass index, and number of cases of primary and secondary infertility in both the groups showed no statistically significant difference. Multi-follicular development during induction was statistically significantly greater in the clomiphene group (1.27±1.11 versus 2.03±1.65; p=0.041). Ovulation occurred in 24 subjects (80%) in letrozole group and 18 subjects (60%) in the clomiphene group, with a statistically significant difference between the two groups (p=0.024). Pregnancy occurred in 16 subjects (53.33%) in letrozole group and 7 subjects (23.33%) in clomiphene group, which shows statistically significant difference between the two groups (p=0.048).Conclusions: Though number of developing follicles was found statistically significant with clomiphene citrate but ovulation rate and pregnancy rate were higher with letrozole group. Therefore, letrozole is a safe and better alternative for ovulation induction in patients of anovulatory PCOS, and it may be considered as a first line treatment for ovulation induction in these patients.

Letrozole: an emerging array of hope for infertile women

Ovulation induction has been a major breakthrough in the management of female infertility since many decades. Letrozole, an aromatase inhibitor has been used as a potential therapy for ovulation induction. A large number of clinical evidences have been emerging which cite the beneficial role of Letrozole in conditions like anovulatory infertility, polycystic ovary syndrome (PCOS), unexplained infertility and an incipient role in endometriosis- related infertility with regards to higher live-birth rates. Letrozole is a superior alternative to Clomiphene citrate (CC) which has been used conventionally as ovulation inducer. Clomiphene citrate has certain well-defined disadvantages, whereas Letrozole overcomes these limitations to a reasonable extent. The peripheral anti-estrogenic effect of CC leads to prolonged depletion of estrogens receptors, adversely affecting endometrial growth and development as well as quantity and quality of cervical mucus. Persistent blockade of estrogen receptor leads to CC resistance and is associated with reduced ovulation and pregnancy rates. Available evidences suggest Letrozole is superior to CC owing to the lack of persistent anti-estrogenic action due to its short half- life and lack of action on estrogen receptors. This typically leads to monofollicular growth and also higher live birth rates. The current evidences suggest that Letrozole can be placed as first line therapy for the management of infertility due to PCOS and unexplained infertility.

Effects of clomiphene citrate on seminal parameters in idiopathic oligospermia: a single blinded prospective randomized controlled trial

Background: About 15% married couples face problem of infertility of which male factor is implicated in 20% of them. In about 30% infertile men no causative factor is found and the condition is termed “Idiopathic”. They are often treated by empirical medications or Assisted Reproductive Technologies (ART) although success in few; our present study is carried on effects of clomephene citrate on seminal parameters in idiopathic oligospermia.Methods: This single blinded prospective randomized controlled trial was conducted at the infertility clinic with 200 idiopathic oligospermic men (sperm count <15 millions/ ml of ejaculate) after fulfilling inclusion and exclusion criteria and were alternately allocated into two equal groups - “Group C” receiving clomephene citrate tablets and “ Group P” receiving placebo after concealment. Semen analysis data were collected at baseline and every month and three months of completion of treatment and were summarized by routine descriptive statistical analysis.Results: The demographic characteristics like mean age is comparative in both groups but duration of infertility of >2 years is more in group C than group p (4.3±3.06 versus 4.1±2.57). The semen volume, spermatozoa count, sperm motility and not normal form are all increased after three months of treatment in group C as are biochemical parameters like total testosterone and serum FSH, LH and as also pregnancy rate (22% versus 4%).Conclusions: This study showed clomiphene citrate treatment protocol is inexpensive, relatively safe and easy to administer and improves semen volume, sperm count and sperm motility but not sperm morphology by increasing serum testosterone, FSH and LH in male and resulting in improved pregnancy rate in female partners.

Management of Anabolic Steroid-Induced Infertility: Novel Strategies for Fertility Maintenance and Recovery

There is often inherent conflict in the overlapping fields of male fertility and andrology. While the goal of all male fertility specialists is to facilitate and preserve biologic paternity, many practitioners also care for a significant number of patients suffering from hypogonadism. Exogenous testosterone administration, the gold standard for the management of these patients, almost universally impairs spermatogenesis and can even completely eradicate it in some men. With steady increases in both the incidence of hypogonadism and average paternal age, practitioners are now encountering hypogonadal men who desire future fertility or men suffering the effects of earlier androgenic anabolic steroid use with increasing frequency. In this manuscript, we review management strategies for these complex patients and explore novel medications that may be of use in this population.

Comparative evaluation of different cost effective ovulation induction drugs and their effect on follicular growth, endometrial thickness and pregnancy outcome

Background: Ovulatory dysfunction is a common cause of female infertility, occurring in up to 20 - 30% of infertile women. The most commonly prescribed ovulation drugs are clomiphene citrate (CC), tamoxifen, aromatase inhibitors (such as letrozole) and gonadotropins. Objective of the study was to evaluate the efficacy of clomiphene citrate, letrozole and tamoxifen for ovulation induction in anovulatory infertility.Methods: Randomized open label interventional clinical trial. Patients were randomized to 3 drug groups. After baseline investigations, they were subjected to ovulation induction and then USG monitoring of follicular growth and ovulation. The primary outcome measured was occurrence of conception. Secondary outcome was effect on endometrial thickness and ovulation rate.Results: In the study, letrozole group showed 100% mono-follicular response. Mid cycle endometrial thickness in about 17% of cases in CC group is ≤8 mm. But all the cases in tamoxifen and letrozole group have ET >8 mm. This difference is statistically significant. The ovulation and conception rates are highest in letrozole group but the difference was not statistically significant.Conclusions: Letrozole produces higher mid cycle endometrial thickness, 100% mono follicular development than clomiphene and tamoxifen. This difference is found to be statistically significant. Ovulation rate and conception rate is highest in letrozole group. But there is no statistically significant difference among the three drugs.

Clomiphene citrate plus N-acetyl cysteine versus letrozole for induction of ovulation in infertile patients with polycystic ovarian disease: a randomized clinical trial

Background: Polycystic ovarian disease (PCOD), a common endocrine disorder with multisystem affection, is the most common cause of anovulatory infertility. Our objective is to evaluate the effect of using clomiphene citrate (CC) plus N-acetyl cysteine (NAC) versus letrozole in ovulation induction in infertile patients with PCOD.Methods: Reproductive-aged infertile women either primary or secondary diagnosed as PCOD according to Rotterdam criteria, 2003 were considered for enrollment. Eligible women for were recruited and randomized (1:1) to receive either CC 100 mg plus NAC 600 mg (CC+NAC arm) or letrozole 5 mg (NCT03241472, clinicaltrials.gov). All medications were started from day 3 of the menstrual cycle for 5 days. The primary outcome was the ovulation rate in both groups. Secondary outcomes included the mid-cyclic endometrial thickness, ovarian hyperstimulation, and clinical pregnancy and miscarriage rates.Results: One hundred ten patients were enrolled and randomized to CC+NAC arm (n=55) or letrozole (n=55). The ovulation rate in patients in letrozole arm was significantly higher than CC+NAC arm (71.8% versus 53.2%, p=0.01). Additionally, endometrial thickness was higher in letrozole arm (mean±SD: 11.46±1.61 versus 9.0±1.13, p=0.031). However, no statistical significant difference with regarding the ovarian hyperstimulation rate (1.8% versus 3.6%, p=0.157), clinical pregnancy rate [3/19 patients (27.3%) versus 19/55 (34.5%), p=0.409] and miscarriage rate [4/15 patients (26.7%) versus 19/55 (15.8%), p=0.317] in CC+NAC versus letrozole groups respectively.Conclusions: Addition of NAC to CC in ovulation induction leads to comparable pregnancy rate as letrozole. However, letrozole produces high ovulation rate and the better mid-cyclic endometrial thickness.

Comparative study of laparoscopic ovarian drilling and medical treatment in polycystic ovarian disease

Background: To evaluate the result after medical treatment and laparoscopic ovarian drilling in PCOS patients and to compare the results of these two methods.Methods: In this prospective study 50 women with polycystic ovarian disease, were divided into two group,25 women received medical treatment and 25 women received surgical (laparoscopic ovarian drilling) treatment. Effect of treatment on ovulation, menstruation, fertility and androgen level was determined 3 month after therapy.Results: There was significant increase in ovulation and fertility, decrease in androgen levels and decrease in LH/FSH in individual groups when compared with pretreatment levels but difference between groups A and B was not statistically significant for these parameters.Conclusions: Medical treatment and laparoscopic ovarian drilling are equally effective in treating the women of polycystic ovarian disease. Result of both the treatment are similar in this study. However medical treatment should be the first line therapy, it has significant benefit for use in OPD, low cost, no hospital stays and convenience to the patient.

A study for evaluation of two protocols comprising of clomiphene citrate, human menopausal gonadotropin with or without follicle stimulating hormone for ovulation induction in patients with infertility for intrauterine insemination

Background: To compare two protocols comprising of FSH/CC/HMG and CC/HMG for ovulation induction and IUI in women with infertility.Methods: 60 women with unexplained infertility were randomized using sequentially numbered opaque envelope method. Group A received inj FSH 150 units on day 2 of menstrual cycle and clomiphene citrate 100 mg from day 3-7, followed by injection HMG 150 units on day 9 of menstrual cycle. Group B received clomiphene citrate 100 mg from day 3-7, and HMG 150 units on day 7 and 9 of the menstrual cycle.  Ovulation triggered with hCG 5000 units when dominant follicle was 18mm. Single IUI was done 36-42 hours afterwards.Results: Pregnancy occurred in 3 out of 30 women in 116 cycles Group A (with FSH) with a pregnancy rate of 10 percent, and 2.8% per cycle. In group B (without FSH) pregnancy occurred in 3 out of 30 women in 117 cycles with pregnancy rate of 10 percent, and 2.6% per cycle. The number of follicles per cycle was 1.36 and follicle size was 18.57 mm in group A. While in Group B numbers of follicles per cycle were 1.22, with average size of 18.9mm. Mean endometrial thickness was 7.7mm in Group A and 6.37 in Group B (p=.01, significant). Mild OHSS was observed in one woman in Group B. No other side effects were observed in both the groups.Conclusions: The controlled ovarian stimulation regimes used in this study are equally effective, easy to administer, require less intensive monitoring and fewer medications, with little risk of OHSS and multiple gestation.

Tetrapleura tetraptera Extract Inhibited Luteinizing Hormone and Estrogen Secretion in Clomiphene Citrate Treated Female Wistar Albino Rats

Tetrapleura tetraptera stem bark has been reported to cause inhibition of luteinizing hormone release in cultured rat pituitary cells. Hence, we investigated the effects of Tetraptera tetrapleura pod extract on follicle stimulating hormone, luteinizing hormone, cortisol, progesterone and estrogen. Thirty non-pregnant female wistar albino rats were divided into group A - D. Group A rats were used as Control. Group B rats were administered 1 mg/kg/day of clomiphene citrate orally. Group C rats were administered 200 mg/kg of extract only, whereas group D rats were administered 1 mg/kg /day of Clomiphene citrate plus 200 mg/kg of extract. At the end of 14 days experiment, group A, B and D were found in proestrus phase and group C in diestrus phase. FSH and cortisol levels remained unchanged. Group C and D rats produced significant reduction (P < 0.05) in LH and estrogen levels in prolonged proestrus and normal diestrus respectively. Progesterone level was significantly high (P < 0.05) in the group C rats. The reduced LH level could be due to the anti-estrogenic effect of extract during proestrus when LH secretion is expected to surge. But co-administration resulted in high progesterone secretion, suggesting extract may have influenced progesterone secretion in group D rats simultaneously administered with clomiphene citrate and extract. The above findings indicated that Tetrapleura tetraptera pod extracts inhibited luteinizing hormone and estrogen even when co-administered with clomiphene citrate.